US2433489A - Production of amidines - Google Patents
Production of amidines Download PDFInfo
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- US2433489A US2433489A US568070A US56807044A US2433489A US 2433489 A US2433489 A US 2433489A US 568070 A US568070 A US 568070A US 56807044 A US56807044 A US 56807044A US 2433489 A US2433489 A US 2433489A
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- benzenesulphonate
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- 238000004519 manufacturing process Methods 0.000 title description 6
- 150000001409 amidines Chemical class 0.000 title description 5
- 239000000047 product Substances 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 15
- WWLOCCUNZXBJFR-UHFFFAOYSA-N azanium;benzenesulfonate Chemical compound [NH4+].[O-]S(=O)(=O)C1=CC=CC=C1 WWLOCCUNZXBJFR-UHFFFAOYSA-N 0.000 description 14
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 11
- 238000002844 melting Methods 0.000 description 11
- 230000008018 melting Effects 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 150000002825 nitriles Chemical class 0.000 description 9
- 239000002253 acid Substances 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 239000013078 crystal Substances 0.000 description 7
- -1 arallzyl Chemical group 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- IIIQERYTCXZYOX-UHFFFAOYSA-N benzenesulfonic acid;4-methylaniline Chemical compound CC1=CC=C(N)C=C1.OS(=O)(=O)C1=CC=CC=C1 IIIQERYTCXZYOX-UHFFFAOYSA-N 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 4
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 4
- 239000000155 melt Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 3
- 229940075930 picrate Drugs 0.000 description 3
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 125000001174 sulfone group Chemical group 0.000 description 3
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 3
- XCSGHNKDXGYELG-UHFFFAOYSA-N 2-phenoxyethoxybenzene Chemical compound C=1C=CC=CC=1OCCOC1=CC=CC=C1 XCSGHNKDXGYELG-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- YPANHENUZZNPMI-UHFFFAOYSA-N C1(=CC=CC=C1)S(=O)(=O)O.C(C1=CC=CC=C1)(=N)N Chemical compound C1(=CC=CC=C1)S(=O)(=O)O.C(C1=CC=CC=C1)(=N)N YPANHENUZZNPMI-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 150000004982 aromatic amines Chemical group 0.000 description 2
- NGYOVXUBIWJNIU-UHFFFAOYSA-N benzenesulfonate;phenylazanium Chemical compound NC1=CC=CC=C1.OS(=O)(=O)C1=CC=CC=C1 NGYOVXUBIWJNIU-UHFFFAOYSA-N 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- OJEIWPNHPIEXOZ-UHFFFAOYSA-N benzenesulfonic acid N'-(4-nitrophenyl)benzenecarboximidamide Chemical compound C1(=CC=CC=C1)S(=O)(=O)O.[N+](=O)([O-])C1=CC=C(C=C1)NC(C1=CC=CC=C1)=N OJEIWPNHPIEXOZ-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 150000003460 sulfonic acids Chemical class 0.000 description 2
- MBDUIEKYVPVZJH-UHFFFAOYSA-N 1-ethylsulfonylethane Chemical compound CCS(=O)(=O)CC MBDUIEKYVPVZJH-UHFFFAOYSA-N 0.000 description 1
- ANPBNAUKOUYEGJ-UHFFFAOYSA-N 4-(methylsulfonyl)benzenecarboximidamide Chemical compound CS(=O)(=O)C1=CC=C(C(N)=N)C=C1 ANPBNAUKOUYEGJ-UHFFFAOYSA-N 0.000 description 1
- FARXIDYHJAANGP-UHFFFAOYSA-N 4-methylsulfonylbenzonitrile Chemical compound CS(=O)(=O)C1=CC=C(C#N)C=C1 FARXIDYHJAANGP-UHFFFAOYSA-N 0.000 description 1
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- GGNHGQLDJQRANG-UHFFFAOYSA-N C(#N)C1=CC=C(C=C1)S(=O)(=O)[O-].[NH4+] Chemical compound C(#N)C1=CC=C(C=C1)S(=O)(=O)[O-].[NH4+] GGNHGQLDJQRANG-UHFFFAOYSA-N 0.000 description 1
- CQCZIONPRBOYLP-UHFFFAOYSA-N C1(=CC=CC=C1)S(=O)(=O)O.C1(=CC=CC=C1)NC(C1=CC=CC=C1)=N Chemical compound C1(=CC=CC=C1)S(=O)(=O)O.C1(=CC=CC=C1)NC(C1=CC=CC=C1)=N CQCZIONPRBOYLP-UHFFFAOYSA-N 0.000 description 1
- 101100231508 Caenorhabditis elegans ceh-5 gene Proteins 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 1
- PYDHQNRJUFGVJL-UHFFFAOYSA-N azanium;3-nitrobenzenesulfonate Chemical compound [NH4+].[O-][N+](=O)C1=CC=CC(S([O-])(=O)=O)=C1 PYDHQNRJUFGVJL-UHFFFAOYSA-N 0.000 description 1
- APCTVOOGAFVFBN-UHFFFAOYSA-N benzenesulfonate;methylazanium Chemical compound [NH3+]C.[O-]S(=O)(=O)C1=CC=CC=C1 APCTVOOGAFVFBN-UHFFFAOYSA-N 0.000 description 1
- BJAARZVFNFJHAY-UHFFFAOYSA-N benzenesulfonic acid;phenylmethanamine Chemical compound NCC1=CC=CC=C1.OS(=O)(=O)C1=CC=CC=C1 BJAARZVFNFJHAY-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- NWSUEGIXYXLCIR-UHFFFAOYSA-N hydron;4-methylsulfonylbenzenecarboximidamide;chloride Chemical compound Cl.CS(=O)(=O)C1=CC=C(C(N)=N)C=C1 NWSUEGIXYXLCIR-UHFFFAOYSA-N 0.000 description 1
- 201000006747 infectious mononucleosis Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- QDVFAGFTHUWITN-UHFFFAOYSA-N methylsulfonylmethane;hydrochloride Chemical compound Cl.CS(C)(=O)=O QDVFAGFTHUWITN-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- XRPNFHZMXJLYKS-UHFFFAOYSA-N n'-benzyl-2-phenylethanimidamide Chemical compound C=1C=CC=CC=1CN=C(N)CC1=CC=CC=C1 XRPNFHZMXJLYKS-UHFFFAOYSA-N 0.000 description 1
- 238000013021 overheating Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/45—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by at least one doubly—bound oxygen atom, not being part of a —CHO group
Description
li ec. 3%, l4?
Patented PRODUCTION OF AMIDINIES Wallace Frank Short and Peter Oxley, Nottingham, England, asslgnors to Boots Pure Drug Company L mited, Nottingham, England, a
company of Great Britain No Drawing, Anplication December 13, 1944, Serial No. 568,070. in Great Britain January 8 s. (Gil. 260501) This invention relates to the production of amidines and its main object is to provide a new method for the production of this class of compound which is generally applicable.
Several methods have already been used for lhe sulohonic acids of which the ammonium salts (RSOaNHQ are used may be such that R is either an alkyl, arallzyl, or aryl group. The nitriles (RUN) which may be used in carrying out the process in accordance with the invention may be such that R may be a substituted or un substituted allryl, arallsyl, aryl or heterocyciic group and, if the boiling point of the nitrile employed is not sufficiently high to enable the reaction to be carried out under atmospheric pressure, the reacting substances may be heated to the requisite temperature in a closed vessel. Furthermore, substances which may be regarded as potential sources of nitriles under the conditions of the reaction, for example, carboxylic amides may be used in the reaction.
Instead of ammonium salts of sulphonic acids, salts of primary mono amines and secondary arylamines with sulphonic acids may be usedresulting in the formation of monoor di-N- substituted amidiues. Where it is'convenient the salts need not be preformed but a mixture of an amine and a sulphonic acid may be used in the reaction.
duced in the above manner have application in chemotherapy.
Example 1 In the manufacture of p-sulphonamidobenzamidine 'D-NHaSOmCcHaCUNHLNI-Iz. 50 gms. of p-sulphonamidobenzonitrile is melted and heated to about 200 C. with gentle stirring, o prevent local overheating. gms.. that is 1.46 molecules, of dry ammonium benzenesulphonate is then added as rapidly as it will dissolve and during this operation which takes about 5 minutes, the temperature of the melt is raised to 250 C. The temperature is maintained at 250 to 255 C. for two hours and the resulting brown liquid is then allowed to solidify and it is then dissolved in 300 c. c. of hot, water. The solution is cooled to room temperature. stirred with 1 gm. of decolourislng charcoal and filtered. The iiitrate is warmed to about 40 C. and an excess oi 0.880 ammon a-25 c. c. or about 1.55 moleculesis added to precipitate p-sulphonamidobenzamidine in a cryst ll ne, easilv filterable form. The product is collected with suction, washed thoroughly with water and dried, when it melts at about 215 C. it may be converted" immediately into a salt, such as the hydrochloride by solution in the appropriate acid.
The ammoniacal liquor (containing ammonium benzenesulfonate) from which the amidine has been removed may be evaporated to constant weight and used to react with a second amount of 50 arms. 05; nitrile.
The process of recovering the ammonium ben zenesulphonate and using it with further nitrile may be repeated.
in variants of the above example, other ammonium sulphonates instead of ammonium benzenesulphonate are caused to react with p-sulphamidobenzonitrile. Thus ammonium toluenep sulphonate, ammonium-m-nitrobenzenesulphonate, ammonium naphthalene-B-sulphonate or ammonium methanesulphonate may be used under similar conditions and the products isolated as described in the above example. l
The following are examples of processes according to the invention, in which other nitrlles are employed.
Example 2 In the preparation of N-(p-sulphonamidophenly) -be nzamidine 2 parts by weight of benzenitrlle, 3.4 parts by weight of sulphanilamide and 3.5 parts by weight of benzenesulphonic acid are heated together at 230 C. for ill minutes. After cooling, the product is dissolved in aqueous-alco- 3 hol andthe precipitate formed on addition of ammonia is separated and crystallised from alcohol. yielding crystals with a melting point of 241- 242 C. (Found, N, 15.4% CnHnOzNsS requires N, 15.27%).
Example 3 In the manufacture of benzamidine-p-sulphonic acid, ammonium p-cyanobenzenesulphonate is heated alone at a temperature of about 310 C. for about an hour. In this case, the single starting material contains both the necessary functional groups. The product is isolated by recrystallisation from water.
Example 4 In the preparation of benzamidine benzenesulphonate, 10 parts by weight of benzonitrile and 17 parts by weight of ammonium benzenesulphonate are heated together in a sealed tube at 250 C. for two hours. The product is cooled and recrystallised from water, yielding colourless crystals of benzamidine benzenesulphonate, with a melting point of 175-1755 C.
Example 5 Example 6 In the preparation of undecane1:11-diamidine picrate, 2 parts by weight of lill-dicyanoundecane and 7 parts by weight of ammonium benzenesulphonate are heated together at 260 C. for three hours. The product is cooled, dissolved in alcohol, and mixed with a, solution of picric acid and thus converted to the picrate which separates. After recrystallisation from methyl alcohol it melts at 192 C.
Example 7 In the preparation of 4-amidino-4'-cyanowp-diphenoxy-ethane benzenesulphonate, 5.28 parts by weight of 4:4'-dicyano-a:p diphenoxyethane and 3.50 parts by weight of ammonium benzenesulphonate are heated together at 260 C. for 2 hours. After crystallisation from water 4 amidino-4'-cyano-:B-diphenoxyethane benzenesulphonate is obtained in crystals with a melting point of 239 C. The picrate obtained therefrom has a melting point of 202 C. (Found N, 16.44% C22H1809N6 requires N, 16.47%.
Example 8 In the preparation of 4:4-diamidino-a:p diphenoxyethane benz'enesulphonate 5.28 parts by weight of 4:4'-dicyano-a:fl-diphenoxyethane and 10.5 parts by weight of ammonium benzenesulphonate are heated together at- 260 for 3 hours. The product is crystallised from water.
Example 9 In the preparation of p-amidinophenyl methyl sulphone hydrochloride 18.1 parts by weight of p-cyanophenyl methyl sulphone and 21 parts by weight of ammonium benzenesulphonate are heated together at 260 C. for 1 hour. After cooling, the product is dissolved in hot water and the solution is filtered, cooled to ca. 60 C. and then poured into a stirred mixture of sodium hydroxide solution and ice. The solid product which separates is filtered off and dissolved in dilute hydrochloric acid. The solution is filtered and cooled while excess sodium hydroxide solution is added. The p-amidinophenyl methyl sulphone which i precipitated is filtered oil and dissolved in dilute hydrochloride acid so that the pH of the solution is 6.5-7.0. The solutionis then evaporated to dryness and pamidinophenyl methyl sulphone hydrochloride is obtained.
Example 10 In the preparation of p-amidinophenyl ethyl sulphone hydrochloride 5 parts by weight of pcyanophenyl ethyl sulphone and 5 parts by weight of ammonium benzenesulphonate are heated together at 225 C. for 4 hours. The product is isolated as described in Example 9 and p-amidinophenyl ethyl sulphone hydrochloride is obtained in crystals with a melting point of 253 C. (Found N, 11.45% C9H1302N2SC1 requires N, 11.3%.) I
Example 11 In the preparation of p-amidinodiphenyl sulphone benzenesulphonate 50 parts by weight of p-cyanodiphenyl sulphone and 44 parts by weight of ammonium benzenesulphonate are heated together at 260-270 C. for 1% hours. From the product p-amidinodiphenyl sulphone benzenesulphonate is isolated by crystallisation from water.
Example 12 In the preparation of ppf-diamidinodiphenylsulphone dihydrochloride 5 parts by weight of pp-dicyanodiphenylsulphone and 15 parts by weight of ammonium benzenesulphonate are heated together at 270 C. for 1 hour. The product is isolated as described in Example 9 and pp-diamidinodiphenylsulphone dihydrochloride is obtained in crystals with a melting point of 300-302 C.
Example 13 Example 14 In the preparation of p-naphthamidine hen-- zenesulphonate, 2 parts by weight of fl-naphthonitrile and 5 parts by weight of ammonium benzenesulphonate are heated together at 250 C. for two hours. The product is cooled and crystallised from water, in the form of colourless crystals melting at 203 C. The free amidine having a melting point of 136 C. crystallises from an alcoholic solution of the benzenesulphonate on adding the theoretical amount of aqueous sodium hydroxide.
Example 15 In the preparation of a-amidinopyridine 5.2 parts by weight of e-cyanopyridine and 12 parts Example 16 In the preparation of N-p-tolylbenzamidine benzenesulphonate, a mixture of 2 parts by weight of'benzonitrile and 5.3 parts by weight, or 1 molecule, of p-toluidine benzenesulphonate is heated in a bath at 240 C. until the internal temperature of the mixture rises to 240 C. The product is then cooled and crystallised from water. In this and the next example, the free amidine may be prepared by adding aqueous ammonia to an aqueous or alcoholic solution of the benzenesulphonate.
If in this example, p-toluidine benzenesulphonate is replaced by the corresponding amount of aniline benzenesulphonate, N-phenyl benzamidine benzenesulphonate is obtained.
Example 17 In the preparation of 'NN'-di-p-tolylbenzamidine benzenesulphonate, a mixture of 2 parts by weight of benzonitrile and 11 parts by weight, or 2 molecules, of p-toluidine benzenesulphonate is heated at 270 C. for one hour. The product is then crystallised from water and melts at 217 C. The mother liquor contains a trace of N-ptolylbenzamidine benzenesulphonate.
If in this example also, p-toluidine benzenesulphonate is replaced by the corresponding amount of aniline benzenesulphonate, INN- diphenyl benzamidine benzenesulphonate is obtained.
Example 18 In the preparation of N-p-nitrophenylbenzamidine benzenesulphonate, 6 parts by weight of p-nitraniline benzenesulphonate and 2 parts by weight of benzonitrile are heated together at 200 C. for ten minutes and the product recrystallised from water when N-p-nitrophenylbenzamidine benzenesulphonate separates in orange cyrstals. From these p-nitrophenylbenzamidine with a melting point of 167 C. may be obtained.
Example 19 In the preparation of N-p-tolylphenylacetamihydroinde solution with cooling, and extracted with chloroform. After evaporation of the chloroform the residue is dissolved in dilute acetic acid and N-methylphenylaceta'midine reineckate is precipitated by adding a solution of ammonium reineckate, in crystalline form with a melting point of 134 C. (Found SCN, 49.66%. CiIiHmNaStCr requires SCN, 49.68%.)
Example 21 In the preparation of N-benzylphenylacetamidine 6 parts by weight of benzyl cyanide and 15 parts by weight of benzylamin benzenesulphonate are heated together at 265-270 C. for two hours. After cooling the product is dissolved in water, excess 5N sodium hydroxide solution is added with cooling and the mixture is extracted with chloroform. Th basic product is removed from the chloroform solution by extraction with dilute hydrochloric acid and this acid solution is then made alkaline with sodium hydroxide solution with cooling, and extracted with chloroform.
The residue after evaporation of the chloroform is crystallised from light petroleum and N-benzylphenylacetam-idine is obtained in crystals with a melting point of 93 C.
Example 22 In the preparation of NzN-diphenylbenzamidine benzenesulphonate, 2 parts by weight of benzonitrile, 3.4 parts by weight of diphenylamine, and 3.2 parts by weight of benzenesulphonic acid (the two latter compounds being in approximately equivalent amounts), are heated together at 210 C. for twenty minutes. product is cooled, triturated with acetone to remove any unreacted diphenylamine, and the residue recrystallised from water.
dine benzenesulphonate, 2 parts by weight of benzyl cyanide (CeH5.CHz.CN) and 6 parts by weight of p-toluidine benzenesulphonate, are heated together as described in Example 16 after which the cooled product is recrystallised from water.
Example 20 In the preparation of Nmeth yl-phenylacetamidine reineckate 8 parts by weight of benzylcyanide and 14 parts by weight of methylamine benzenesulphonate are heated together at 265- 270 C. for 2 hours. After cooling the product is dissolved in water, excess sodium hydroxide solution is added with cooling, and the mixture is The following is an example of a process according to the invention in which a carboxylic amide is used.
Example 23 ber of the class consisting of alkyl, aralkyl, aryl and heterocyclic radicals, into an amidine compound the step which consists ln heating the said nitrile at a temperature of at least about 200 C.
with a sulphonic acid salt derived from a base selected from the class consisting of ammonia, primary amines and secondary arylamines and a sulphonic acid selected from the class consisting I of aliphatic, araliphatic and aromatic sulphonic extracted with chloroform. The basic product is removed from the chloroform solution by extraction with dilute hydrochloric acid and this acid solution is then made alkaline with sodium acids.
2. Process as defined in claim 1 in which the nitrile is a sulfonamidobenzonitrile.
3. Process as defined in claim 1 in which the sulfonic acid salt is ammonium benzene sulfonate. I
4. Process a defined in claim 1 in which a substance capable of yielding the nitrile is supplied to the reaction mixture.
5. Process as defined in claim 1 in which a substance capable of yielding the sulfonic acid salt is supplied to the reaction mixture.
The
7 6. Process as defined in claim 1 in which a sin- 81a substance containing both the nitrile and the sulionic acid groups is supplied to the reaction mixture.
WALLACE FRANK SHORT. PETER om.
REFERENCES CITED The following references are of record in the file of this patent:
UNITED STATES PATENTS 10 pages 360, 363, 373 (1944) (abstracts of articles Number Name Date 1,693,055 Schoeller Nov. 27, 1928 2,255,090 Tinker et a1 Sept. 9, 1941 2,277,861 Ewins et a1 Mar. 31, 1942 2,375,611 Barber et a1 May 8, 1945 of earlier date).
Evans et ai., Lancet, Oct. 21, 1944, 524.
p es
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB2433489X | 1944-01-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2433489A true US2433489A (en) | 1947-12-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US568070A Expired - Lifetime US2433489A (en) | 1944-01-27 | 1944-12-13 | Production of amidines |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US2433489A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2736748A (en) * | 1950-09-11 | 1956-02-28 | Boots Pure Drug Co Ltd | N-(2'-naphthyl) amidinoalkanes |
| US3105853A (en) * | 1959-11-30 | 1963-10-01 | Monsanto Canada Ltd | Bis |
| WO2003084938A2 (en) * | 2002-04-10 | 2003-10-16 | Orchid Chemicals & Pharmaceuticals Limited | Pyrimidone derivatives useful for the treatment of inflammatin and immunological diseases |
| RU2690184C1 (en) * | 2018-10-29 | 2019-05-31 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Санкт-Петербургский государственный химико-фармацевтический университет" Министерства здравоохранения Российской Федерации (ФГБОУ ВО СПХФУ Минздрава России) | Method of producing n-(4-sulphamoylphenyl)benzamidine |
| RU2693475C1 (en) * | 2019-03-14 | 2019-07-03 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Санкт-Петербургский государственный химико-фармацевтический университет" Министерства здравоохранения Российской Федерации (ФГБОУ ВО СПХФУ Минздрава России) | Analgesic and anti-inflammatory agent with antimicrobial activity |
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|---|---|---|---|---|
| US1693055A (en) * | 1926-08-02 | 1928-11-27 | Firm Chem Fab Auf Actien Vorm | Pharmaceutical preparations and process of making same |
| GB507565A (en) * | 1937-12-10 | 1939-06-12 | May & Baker Ltd | Process for the preparation of amidine derivatives |
| US2255090A (en) * | 1940-02-13 | 1941-09-09 | Du Pont | Inhibiting the gas fading of dyed acetate silk |
| US2277861A (en) * | 1937-12-10 | 1942-03-31 | May & Baker Ltd | Process for the preparation of diamidine derivatives |
| US2375611A (en) * | 1941-08-19 | 1945-05-08 | May & Baker Ltd | Production of amidines |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1693055A (en) * | 1926-08-02 | 1928-11-27 | Firm Chem Fab Auf Actien Vorm | Pharmaceutical preparations and process of making same |
| GB507565A (en) * | 1937-12-10 | 1939-06-12 | May & Baker Ltd | Process for the preparation of amidine derivatives |
| US2277861A (en) * | 1937-12-10 | 1942-03-31 | May & Baker Ltd | Process for the preparation of diamidine derivatives |
| US2255090A (en) * | 1940-02-13 | 1941-09-09 | Du Pont | Inhibiting the gas fading of dyed acetate silk |
| US2375611A (en) * | 1941-08-19 | 1945-05-08 | May & Baker Ltd | Production of amidines |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2736748A (en) * | 1950-09-11 | 1956-02-28 | Boots Pure Drug Co Ltd | N-(2'-naphthyl) amidinoalkanes |
| US3105853A (en) * | 1959-11-30 | 1963-10-01 | Monsanto Canada Ltd | Bis |
| WO2003084938A2 (en) * | 2002-04-10 | 2003-10-16 | Orchid Chemicals & Pharmaceuticals Limited | Pyrimidone derivatives useful for the treatment of inflammatin and immunological diseases |
| WO2003084938A3 (en) * | 2002-04-10 | 2004-02-05 | Orchid Chemicals & Pharm Ltd | Pyrimidone derivatives useful for the treatment of inflammatin and immunological diseases |
| RU2690184C1 (en) * | 2018-10-29 | 2019-05-31 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Санкт-Петербургский государственный химико-фармацевтический университет" Министерства здравоохранения Российской Федерации (ФГБОУ ВО СПХФУ Минздрава России) | Method of producing n-(4-sulphamoylphenyl)benzamidine |
| RU2693475C1 (en) * | 2019-03-14 | 2019-07-03 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Санкт-Петербургский государственный химико-фармацевтический университет" Министерства здравоохранения Российской Федерации (ФГБОУ ВО СПХФУ Минздрава России) | Analgesic and anti-inflammatory agent with antimicrobial activity |
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